Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults
- Madhukar Pai, MD, PhD
Madhukar Pai, MD, PhD
- Professor, Department of Epidemiology, Biostatistics & Occupational Health
- McGill University
- Dick Menzies, MD, MSc
Dick Menzies, MD, MSc
- Professor of Medicine and of Epidemiology & Biostatistics
- Montreal Chest Institute, McGill University
Treatment of individuals with active tuberculosis (TB) is the first priority for tuberculosis control; an important second priority is identification and treatment of individuals with latent tuberculosis infection (LTBI) [1-3].
In most individuals, Mycobacterium tuberculosis infection is contained initially by host defenses, and infection remains latent . However, latent infection has the potential to develop into active disease at any time. Identification and treatment of latent tuberculosis infection can reduce the risk of development of disease by as much as 90 percent  and so has the potential to protect the health of the individuals as well as the public by reducing the number of potential sources of infection [6,7].
There are two major tests for identification of latent tuberculosis infection: the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA) [8,9]. Both tests evaluate cell-mediated immunity.
Use of TST for diagnosis of LTBI in HIV-uninfected patients will be reviewed here. Management of LTBI for patients with HIV or receiving tumor necrosis factor-alpha inhibitors is discussed in detail separately, as are issues related to TB screening in children and treatment of LTBI in HIV-uninfected patients. (See "Treatment of latent tuberculosis infection in HIV-infected adults" and "Latent tuberculosis infection in children" and "Tumor necrosis factor-alpha inhibitors and mycobacterial infections" and "Interferon-gamma release assays for diagnosis of latent tuberculosis infection".)
INDICATIONS FOR TESTING
The goal of testing for latent tuberculosis infection (LTBI) is to identify individuals who are at increased risk for the development of tuberculosis (TB) and therefore would benefit from treatment of LTBI (table 1 and table 2); these include [10-13]:
- World Health Organization. Guidelines on the management of latent tuberculosis infection. WHO, Geneva 2015. http://www.who.int/tb/publications/ltbi_document_page/en/ (Accessed on March 02, 2016).
- Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis 2017; 64:e1.
- Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000; 161:S221.
- Pai M, Behr MA, Dowdy D, et al. Tuberculosis. Nat Rev Dis Primers 2016; 2:16076.
- Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999; 3:847.
- Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004; 350:2060.
- Rieder HL. Interventions for Tuberculosis Control and Elimination. International Union Against Tuberculosis and Lung Disease, 2002.
- Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med 2015; 372:2127.
- Getahun H, Matteelli A, Abubakar I, et al. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J 2015; 46:1563.
- Horsburgh CR Jr, Rubin EJ. Clinical practice. Latent tuberculosis infection in the United States. N Engl J Med 2011; 364:1441.
- Mancuso JD, Tribble D, Mazurek GH, et al. Impact of targeted testing for latent tuberculosis infection using commercially available diagnostics. Clin Infect Dis 2011; 53:234.
- US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 316:962.
- Kahwati LC, Feltner C, Halpern M, et al. Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2016; 316:970.
- Marais BJ, Gie RP, Schaaf HS, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis 2004; 8:392.
- Linas BP, Wong AY, Freedberg KA, Horsburgh CR Jr. Priorities for screening and treatment of latent tuberculosis infection in the United States. Am J Respir Crit Care Med 2011; 184:590.
- Canadian Tuberculosis Standards, 7th Edition 2013. http://www.respiratoryguidelines.ca/tb-standards-2013 (Accessed on November 16, 2016).
- Comstock GW, Edwards LB, Livesay VT. Tuberculosis morbidity in the U.S. Navy: its distribution and decline. Am Rev Respir Dis 1974; 110:572.
- Cheng MP, Abou Chakra CN, Yansouni CP, et al. Risk of Active Tuberculosis in Patients with Cancer: A Systematic Review and Meta-Analysis. Clin Infect Dis 2016.
- Stead WW, To T, Harrison RW, Abraham JH 3rd. Benefit-risk considerations in preventive treatment for tuberculosis in elderly persons. Ann Intern Med 1987; 107:843.
- Kopanoff DE, Snider DE Jr, Caras GJ. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis 1978; 117:991.
- The Online TST/QFT Interpreter. Version 2.0. http://www.tstin3d.com/index.html (Accessed on September 24, 2010).
- Pai M, Kunimoto D, Jamieson F, Menzies D. Diagnosis of Latent TB Infection. In: Canadian Tuberculosis Standards, 7th ed, Menzies D. (Ed), Canadian Lung Association and Public Health Agency of Canada, Ottawa 2013.
- Hoppe LE, Kettle R, Eisenhut M, et al. Tuberculosis--diagnosis, management, prevention, and control: summary of updated NICE guidance. BMJ 2016; 352:h6747.
- COMSTOCK GW, EDWARDS LB, PHILIP RN, WINN WA. A COMPARISON IN THE UNITED STATES OF AMERICA OF TWO TUBERCULINS, PPD-S AND RT 23. Bull World Health Organ 1964; 31:161.
- Menzies D, Doherty TM. Diagnosis of latent tuberculosis infection. In: Reichman and Hershfield's Tuberculosis, a comprehensive international approach, Raviglione MC (Ed), Informa Healthcare USA, New York 2006. p.215.
- DUBOCZY BO, BROWN BT. Multiple readings and determination of maximal intensity of tuberculin reaction. Am Rev Respir Dis 1961; 84:60.
- Froeschle JE, Ruben FL, Bloh AM. Immediate hypersensitivity reactions after use of tuberculin skin testing. Clin Infect Dis 2002; 34:E12.
- FURTHER studies of geographic variation in naturally acquired tuberculin sensitivity. Bull World Health Organ 1955; 12:63.
- Centers for Disease Control and Prevention. Guide to Vaccine Contraindications and Precautions. Department of Health and Human Services. Available at: http://www.cdc.gov/vaccines/recs/vac-admin/downloads/contraindications-guide-508.pdf
- Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med 1999; 159:15.
- Farhat M, Greenaway C, Pai M, Menzies D. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis 2006; 10:1192.
- von Reyn CF, Horsburgh CR, Olivier KN, et al. Skin test reactions to Mycobacterium tuberculosis purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States. Int J Tuberc Lung Dis 2001; 5:1122.
- A World Atlas of BCG Vaccination Policies and Practices http://www.bcgatlas.org/ (Accessed on April 01, 2009).
- Vinkeles Melchers NV, van Elsland SL, Lange JM, et al. State of affairs of tuberculosis in prison facilities: a systematic review of screening practices and recommendations for best TB control. PLoS One 2013; 8:e53644.
- Arshad S, Bavan L, Gajari K, et al. Active screening at entry for tuberculosis among new immigrants: a systematic review and meta-analysis. Eur Respir J 2010; 35:1336.
- Rieder H. What is the role of case detection by periodic mass radiographic examination in tuberculosis control?. In: Toman’s Tuberculosis: Case detection, treatment, and monitoring – questions and answers, 2nd ed, Frieden, T. (Eds), World Health Organization, Geneva 2004. p.72.
- Tarlo SM, Day JH, Mann P, Day MP. Immediate hypersensitivity to tuberculin. In vivo and in vitro studies. Chest 1977; 71:33.
- Youssef E, Wooltorton E. Serious allergic reactions following tuberculin skin tests. CMAJ 2005; 173:34.
- Richard Menzies, MD, MSc, personal communication.
- Jensen PA, Lambert LA, Iademarco MF, et al. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep 2005; 54:1.
- World Health Organization. Guidelines for the prevention of tuberculosis in health care facilities in resource-limited settings. WHO/CDS/TB/99.269. IJTLD 1999.
- Menzies R, Vissandjee B, Rocher I, St Germain Y. The booster effect in two-step tuberculin testing among young adults in Montreal. Ann Intern Med 1994; 120:190.
- Richards NM, Nelson KE, Batt MD, et al. Tuberculin test conversion during repeated skin testing, associated with sensitivity to nontuberculous mycobacteria. Am Rev Respir Dis 1979; 120:59.
- Gordin FM, Perez-Stable EJ, Flaherty D, et al. Evaluation of a third sequential tuberculin skin test in a chronic care population. Am Rev Respir Dis 1988; 137:153.
- Ferebee SH. Controlled chemoprophylaxis trials in tuberculosis. Adv Tuberc Res 1969; 17:28.
- INDICATIONS FOR TESTING
- Risk of new infection
- - General principles
- - Immigrants from high-incidence to low-incidence countries
- Risk of progression to active disease due to underlying conditions
- - General principles
- - Age and risk of drug-induced hepatitis
- TOOLS FOR LTBI TESTING
- Interferon gamma release assays
- Tuberculin skin test
- - Performing the TST
- Adverse reactions
- - Interpreting the TST
- Negative tests
- - False-negative tests
- - Treating negative tests
- Positive tests
- - False-positive tests
- - Treating positive tests
- Healthcare workers
- Allergic reactions
- Managing referrals
- - Repeat and serial testing
- Repeat TST interpretation
- - Booster response
- - TST conversion
- - Definition of positive repeat TST
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS